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Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles
Experimental Therapeutics Center, the Agency for Science, Technology and Research, Singapore 138669, Singapore
Institute of Chemical & Engineering Sciences, Agency for Science, Technology and Research (A*STAR), Singapore 627833, Singapore
* Author to whom correspondence should be addressed.
Received: 24 June 2013; in revised form: 18 July 2013 / Accepted: 18 July 2013 / Published: 22 July 2013
Abstract: The C-terminal domains of the Frizzleds (FZDs) contain a short conserved motif (KTXXXW). It has been demonstrated that FZDs interacted with the PDZ domain of the cytoplasmic proteins such as Dishevelled through this motif and mutations in this motif disrupted Wnt/β-catenin signaling. We carried out structural studies for a peptide derived from the C-terminal domain of the FZD1 in different solvents using circular dichroism and solution NMR spectroscopy. Our results showed that this domain was unstructured in an aqueous solution and formed a helical structure in detergent micelles. Fluorescence studies suggested that the tryptophan residue (W630) in the motif interacted with micelles. The solution structure of the peptide in sodium dodecyl sulfate micelles was determined and an amphipathic helix was identified. This helix may have similar function to the helix 8 of other G protein-coupled receptors.
Keywords: helix 8; Frizzled receptor; detergent micelles; NMR
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Gayen, S.; Li, Q.; Kim, Y.M.; Kang, C. Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles. Molecules 2013, 18, 8579-8590.
Gayen S, Li Q, Kim YM, Kang C. Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles. Molecules. 2013; 18(7):8579-8590.
Gayen, Shovanlal; Li, Qingxin; Kim, Young M.; Kang, CongBao. 2013. "Structure of the C-terminal Region of the Frizzled Receptor 1 in Detergent Micelles." Molecules 18, no. 7: 8579-8590.